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Overview

Uniprot IDQ9NR31
Protein NameSmall COPII coat GTPase SAR1A
Gene NameSAR1A
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
146 TDAISEEKLREIFGL
166 GKGNVTLKELNARPM

Function

Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. The active GTP-bound form inserts into the endoplasmic reticulum membrane where it recruits the remainder of the coat protein complex II/COPII. The coat protein complex II assembling and polymerizing on endoplasmic reticulum membrane is responsible for both the sorting of cargos and the deformation and budding of membranes into vesicles destined to the Golgi (PubMed:23433038, PubMed:32358066, PubMed:36369712). The GTPase activity of SAR1 by controlling the timing of COPII budding regulates the size of the formed vesicles and is important for cargo selection depending on their size (PubMed:32358066). Together with SEC16A, forms the organized scaffold defining endoplasmic reticulum exit sites (ERES), some specific domains of the endoplasmic reticulum where COPII vesicles form (PubMed:17005010). In addition to its role in vesicle trafficking, can also function as a leucine sensor regulating TORC1 signaling and more indirectly cellular metabolism, growth and survival. In absence of leucine, interacts with the GATOR2 complex via MIOS and inhibits TORC1 signaling. The binding of leucine abrogates the interaction with GATOR2 and the inhibition of the TORC1 signaling. This function is completely independent of the GTPase activity of SAR1B (PubMed:34290409)

Protein Sequence

10 MSFIFEWIYN 20 GFSSVLQFLG 30 LYKKSGKLVF 40 LGLDNAGKTT 50 LLHMLKDDRL 60 GQHVPTLHPT 70 SEELTIAGMT 80 FTTFDLGGHE 90 QARRVWKNYL 100 PAINGIVFLV 110 DCADHSRLVE 120 SKVELNALMT 130 DETISNVPIL 140 ILGNKIDRTD 150 AISEEKLREI 160 FGLYGQTTGK 170 GNVTLKELNA 180 RPMEVFMCSV 190 LKRQGYGEGF RWLSQYID

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030127 COPII vesicle coat
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0070971 endoplasmic reticulum exit site
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0032580 Golgi cisterna membrane
Cellular Component GO:0005765 lysosomal membrane
Molecular Function GO:0140785 amino acid sensor activity
Molecular Function GO:0003925 G protein activity
Molecular Function GO:0005525 GTP binding
Molecular Function GO:0003924 GTPase activity
Biological Process GO:1990253 cellular response to leucine starvation
Biological Process GO:0048208 COPII vesicle coating
Biological Process GO:0090110 COPII-coated vesicle cargo loading
Biological Process GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
Biological Process GO:0006886 intracellular protein transport
Biological Process GO:0061024 membrane organization
Biological Process GO:1904262 negative regulation of TORC1 signaling
Biological Process GO:1902953 positive regulation of ER to Golgi vesicle-mediated transport
Biological Process GO:0070863 positive regulation of protein exit from endoplasmic reticulum
Biological Process GO:0003400 regulation of COPII vesicle coating
Biological Process GO:1903432 regulation of TORC1 signaling
Biological Process GO:0016050 vesicle organization

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.